M K Karlsson

Prevalent vertebral deformities predict increased mortality and increased fracture rate in both men and women: a 10-year population-based study of 598 individuals from the Swedish cohort in the European Vertebral Osteoporosis Study.

Abstract The aim of this study was to evaluate whether a prevalent vertebral deformity predicts mortality and fractures in both men and women. In the city of Malmö, 598 individuals (298 men, 300 women; age 50–80 years) were selected from the citys population and were included in the Swedish part of the European Vertebral Osteoporosis Study (EVOS). At baseline the participants answered a questionnaire and lateral spine radiographs were performed. The prevalence of subjects with vertebral deformity was assessed using a morphometric method. The mortality during a 10-year follow-up period was determined through the register of the National Swedish Board of Health and Welfare. Eighty-five men and 43 women died during the study period. The subsequent fracture incidence during the follow-up period was ascertained by postal questionnaires, telephone interviews and by a survey of the archives of the Department of Radiology in the city hospital. Thirty-seven men and 69 women sustained a fracture during the study period. Data are presented as hazard ratios (HR) with 95% confidence interval (95% CI) within brackets. Prevalent vertebral deformity, defined as a reduction by more than 3 standard deviations (SD) in vertebral height ratio, predicted mortality during the forthcoming decade in both men [age-adjusted HR 2.4 (95% CI 1.6–3.9)] and women [age-adjusted HR 2.3 (95% CI 1.3–4.3)]. In men there was an increased mortality due to cardiovascular and pulmonary diseases and in women due to cancer. Prevalent vertebral deformity predicted an increased risk of any fracture during the forthcoming decade in both men [age-adjusted HR 2.7 (95% CI 1.4–5.3)] and women [age-adjusted HR 1.8 (95% CI 1.1–2.9)]. Prevalent vertebral deformity predicted an increased risk of any subsequent fragility fracture in women [age-adjusted HR 2.0 (95% CI 1.1–3.5)]; however, in men the increased risk was nonsignificant [age-adjusted HR 1.9 (95% CI 0.7–5.1)]. In summary, a prevalent vertebral deformity can predict both increased mortality and increased fracture incidence during the following decade in both men and women. We conclude that prevalent vertebral deformity could be used as a risk factor in both genders for mortality and future fracture.

Exercise during growth and bone mineral density and fractures in old age

If exercise is to be recommended during growth, benefits in bone mineral density (BMD) must be maintained in old age and shown to prevent fractures. Our cross-sectional study of soccer players suggests that a high BMD is no longer recorded after retirement and fracture frequency is no less than predicted in old age.

Pregnancy and Lactation Confer Reversible Bone Loss in Humans

Abstract: The influence of pregnancy on bone mineral density (BMD) was evaluated by dual-energy X-ray absorptiometry (DXA) in 73 women (mean age 29 years, range 20–44 years) postpartum. Fifty-five age-matched women served as controls. The influence of lactation was evaluated in 65 of the delivered women who were followed with repeated measurements, a mean of 4.5 ± 0.1 and 11.5 ± 0.1 months after the delivery. The influence of multiple pregnancies was evaluated in 39 premenopausal women (mean age 38 years, range 31–54 years) with a minimum of four pregnancies (range 4–7). Fifty-eight age-matched healthy premenopausal women with a maximum of two pregnancies (range 0–2) served as controls. Data are presented as mean ± SEM. BMD data are adjusted for differences in total fat mass and total lean mass. Lumbar spine BMD was 7.6 ± 0.1% and total body BMD 3.9 ± 0.1% lower in women postpartum compared with controls (both p<0.001). BMD did not decrease significantly in non-breastfeeding mothers. Mothers breastfeeding for 1–6 months decreased femoral neck BMD by 2.0 ± 1.0% during the first 5 months postpartum (p<0.001). No further BMD loss was seen between 5 and 12 months postpartum. Femoral neck BMD 12 months after delivery was 1.3 ± 0.8% lower than after delivery in mothers breastfeeding for 1–6 months (p= 0.05). Mothers breastfeeding for more than 6 months decreased Ward’s triangle BMD by 8.5 ± 1.0% and lumbar spine BMD by 4.1 ± 0.8% during the first 5 months postpartum (both p<0.05). No further BMD loss was seen between 5 and 12 months postpartum. Femoral neck BMD 12 months after delivery was 4.0 ± 1.1% lower and Ward’s triangle BMD 5.3 ± 1.9% lower than after delivery in mothers breastfeeding for more than 6 months (both p<0.05). BMD loss was higher during the first 5 months following delivery in the lactating women compared with the non-lactating women (p< 0.05 comparing lumbar spine BMD loss in lactating mothers versus non-lactating mothers). However, in women with a minimum of four pregnancies the BMD was no lower than in age-matched women with fewer pregnancies. Total duration of lactation was not correlated with the present BMD. In summary, pregnancy seem to confer a low BMD with additional BMD loss during 5 months of lactation. Even if complete restoration in BMD was not reached within 5 months of weaning, women with four pregnancies or more had a BMD no lower than women with two pregnancies or fewer. We conclude that neither an extended lactation period nor multiple pregnancies could be used as a risk factor when predicting women at risk for future osteoporosis.

Long-Term Morbidity and Mortality After a Clinically Diagnosed Vertebral Fracture in the Elderly-a 12- and 22-Year Follow-up of 257 Patients.

The objective of this study was to analyze the long-term morbidity and mortality in patients with a clinically diagnosed vertebral fracture. Seventy men with a mean age of 70 years (range 50–91 years) and 187 women with a mean age of 72 years (range 50–96 years) were radiographically diagnosed as having a vertebral fracture in the thoracic or lumbar spine at the Malmö University Hospital (Sweden) during 1979. At the time of a follow-up examination 12 years later, 56 of the 76 patients who were still alive participated in an investigation that evaluated back pain and subjective health status by a questionnaire. Forty-four of these subjects also participated in a further radiologic examination of the spine. Serving as controls were age- and gender-matched subjects from the Malmö cohort of the European Vertebral Osteoporosis Study (EVOS). A mortality analysis was also conducted, covering 22 years following the baseline fracture. There were more female patients, who, in comparison with the controls, 12 years after the diagnosis, had had back pain during the year preceding the follow-up (72% vs 33%, P < 0.001), had current back pain (42% vs. 19%, P = 0.006), and had a subjectively impaired health status (44% vs. 17%, P < 0.001). The corresponding differences in men reached only a borderline significance, for both back pain during the year preceding the follow-up (60% vs. 28%, P = 0.07) and current back pain (40% vs. 15%, P = 0.09), whereas there was no difference in subjective health status. The incidence of new vertebral fractures in individuals with a clinically diagnosed vertebral fracture during the following 12 years was in men 25 per 1,000 person-years and in women 49 per 1000 person-years. There were more women with a new vertebral fracture at the 12-year follow-up examination who, in comparison with women without a new fracture, had had back pain during the year preceding the follow-up examination (90% vs. 50%, age-adjusted P = 0.02) and had current back pain (65% vs. 21%, age-adjusted P = 0.03). Women with a new vertebral fracture at the 12-year follow-up examination had a higher subsequent mortality rate in the next 10 years [age-adjusted hazard ratio 2.8 (95% CI 1.0–7.9)] as compared with women without. The mortality rate during the 22 years following the diagnosis among the male patients was 111.7 per 1,000 person-years as compared with 73.4 per 1,000 person-years among the male population at risk. The mortality rate among the female patients was 95.1 per 1,000 person-years as compared with 62.0 per 1,000 person-years among the female population at risk. We conclude that a clinically diagnosed thoracic or lumbar vertebral fracture in the elderly can be regarded as a risk factor for subsequent, long-term morbidity, especially in women, and for mortality in both genders.

Bone loss in relation to menopause: a prospective study during 16 years

This prospective study evaluated bone loss in the peri- and postmenopausal period in 156 women followed from age 48 to 64 years. All women were premenopausal at the start of the study. Areal bone mineral density (g/cm(2)) was measured by single-photon absorptiometry (SPA) of the forearm at the 1 cm level (BMD 1 cm) and the 6 cm level (BMD 6 cm) every second year. Onset of menopause (MP) was determined according to the criteria of the World Health Organization (12 months of amenorrhea and elevated follicle-stimulating hormone). At the end of the study, 125 of 156 women (80%) remained. Bone mineral density (BMD) at age 48 years correlated with BMD at age 64 years within the respective region (r = 0.4-0.5, p < 0.001, respectively). There was no BMD loss in the premenopausal period. BMD loss was accelerated at menopause (MP) independent of chronological age. BMD loss was greater during the first 5 years following MP than during the following 6 years (BMD 1 cm 2.4% per year [1.0%-3.9%] vs. 0.4% per year [-0.3%-1.0%], p < 0.01). The quartile of women with late MP (>53.7 years) had greater bone loss during the first 5 years after MP than the quartile of women with early MP (<50.3 years) (p < 0.001). At age 64 years, BMD was no different when comparing the quartile of women with late MP vs. the quartile of women with early MP. Furthermore, there was no correlation between age at menopause and BMD at the age of 64. In summary, among women still menstruating at age 48 years, there was no measurable BMD loss in the premenopausal period. Independent of chronological age, BMD loss accelerated during MP. Rates of loss were highest in the early postmenopausal period. Independent of age at MP, premenopausal women with low age-specific BMD at age 48 years had an increased risk of sustaining low BMD at age 64 years also.

Bone mineral density in athletes during and after career: a comparison between loaded and unloaded skeletal regions

Abstract. Bone mineral density (BMD) was measured in the upper part of the skull, the femoral neck, and the total body by dual energy X-ray absorptiometry in 56 male and 33 female active athletes, 18–40 years of age, together with 64 male ex-weight lifters, 35–79 years of age. The active athletes were compared with 41 male and 54 female controls, the ex-weight lifters with 133 male controls. The purpose of the study was to see if BMD in the upper part of the skull, a region virtually unaffected by physical load, is different in athletes and controls. The male athletes had a 3% higher BMD for the total body and 12% for the hip, whereas the BMD for the upper part of the skull was 10% lower than controls. Corresponding BMD values for the female athletes were 4% higher for total body and 10% for the femoral neck, and the upper part of the skull was 7% lower than in controls. After 65 years of age there was no difference in BMD comparing ex-weightlifters and controls. Using a constructed ratio BMD total body to BMD upper part of the skull, the ex-weight lifters had 10% higher values also after age 65. It appears that bone mass is higher in weight-loaded areas and lower in an unloaded region, such as the upper part of the skull, in exercising athletes. After cessation of the active career, the bone mass approaches that of the controls and after 65 years of age, no difference was found comparing ex-weight lifters and controls. Due to the apparent bone mass shift from unloaded skeletal regions to loaded skeletal regions that seems to take place in active athletes, the constructed ratio, BMD total body to BMD upper part of the skull, seems to discriminate the influence on the skeleton in a more sensitive way than measuring the BMD in defined skeletal regions on their own. By using this constructed ratio, the influence on bone mass of physical exercise early in life is also detectable at older ages.

The duration of exercise as a regulator of bone mass

Exercise is associated with increased peak bone mineral density (BMD). To determine the relationship between the duration of exercise and BMD, we measured BMD of the axial and appendicular skeleton by dual-energy X-ray absorptiometry (DXA), and speed of sound (SOS), broadband attenuation (BUA), and stiffness index by quantitative ultrasound (QUS) of the calcaneus, in 67 active male national soccer players (mean age 23 years, range 17-35), which included 23 premier-league players exercising 12 h/week (range 8-18), 23 third-league players exercising 8 h/week (range 3-18), and 21 sixth-league players exercising 6 h/week (range 2-10). Results were compared with 24 sedentary age- and gender-matched controls and presented as mean +/- SEM. BMD was higher in all weight-bearing regions for the whole group relative to controls (BMD: total body 6.8 +/- 0.7%, leg 9.6 +/- 0.8%, lumbar spine 13.2 +/- 1.2%, femoral neck 12.7 +/- 1.2% [all p < 0.001]; calcaneus SOS 4.2 +/- 0.3%, BUA 8.7 +/- 1.5%, and stiffness index 24.2 +/- 2.0% [all p < 0.01]). No differences were found in head or arm BMD. There were no differences in BMD or QUS measurements when comparing soccer players exercising for different activity durations. Duration of activity correlated with BMD weight-loaded regions and with QUS, provided it was less <6 h/week (p < 0.01 respectively), but not when exercising more frequently. Femoral neck BMD increased by 3.3% across every hour increase in activity in those with 0-6 h of exercise/week and by 0.7% in those exercising more than this (p < 0.01). We conclude that, in national-league soccer, the BMD needed to attain a bone strength commensurate with that of duration of activity is achieved by 6 h of exercise per week. Beyond this, additional exercise confers no higher BMD. The skeleton adapts to the prevalent level of exercise intensity required and no further.

Peripubertal moderate exercise increases bone mass in boys but not in girls: a population-based intervention study

Abstract: On the basis of cross-sectional studies in elite athletes and longitudinal studies, physical activity in growing children has been suggested to enhance bone mineral acquisition and prevent osteoporosis later in life. The level of exercise in most of these studies is not applicable in a population on a day-to-day basis. The aim of this study was to determine whether moderate increased exercise within the school curriculum from age 12 to 16 years would have anabolic bone effects. In a population-based setting of 40 boys and 40 girls the school curriculum was enhanced to physical education 4 times per week for 3–4 years. Controls were 82 boys and 66 girls who had had physical education twice a week over a corresponding period. Both cases and controls were measured at age 16 years. Bone mineral content (BMC), areal bone mineral density (aBMD), bone size (femoral neck width) and volumetric BMD (vBMD) were measured in total body, spine and femoral neck (FN) by dual-energy X-ray absorptiometry. Data are presented as mean ± SD. BMC (8 ± 15%, p= 0.04), aBMD (9 ± 13%, p= 0.002) and vBMD (9 ± 15%, p= 0.001) were all higher in FN in the male intervention group compared with controls. FN bone size was no higher in the intervention group than in the controls. In girls, no differences were found when comparing the intervention group with controls. The results remained after adjusting for confounding factors such as weight, height, milk intake and activity after school. In summary, we report that increased bone mass can be achieved in a population-based cohort of boys (but not in girls) by moderate increased physical activity within the school curriculum from age 12 to 16 years. We speculate that the same results can be seen in girls if intervention starts at an earlier age. We conclude that increasing the physical education content of the Swedish school curriculum may improve bone mass in at least peripubertal boys.

Insulin and free oestradiol are independent risk factors for benign prostatic hyperplasia

The aetiology of benign prostatic hyperplasia (BPH) remains unclear. The objective of the present study was to test the insulin, oestradiol and metabolic syndrome hypotheses as promoters of BPH. The design was a risk factor analysis of BPH in which the total prostate gland volume was related to endocrine and anthropometric factors. The participants studied were 184 representative men, aged 72–76 years, residing in Göteborg, Sweden. Using a multivariate analysis, BPH as measured by the total prostate gland volume correlated statistically significantly with fasting serum insulin (β=0.200, P=0.028), free oestradiol (β=0.233, P=0.008) and lean body mass (β=0.257, P=0.034). Insulin and free oestradiol appear to be independent risk factors for BPH, confirming both the insulin and the oestradiol hypotheses. Our findings also seem to confirm the metabolic syndrome hypothesis. The metabolic syndrome and its major endocrine aberration, hyperinsulinaemia, are possible primary events in BPH.

Physical Activity Increases Bone Size in Prepubertal Boys and Bone Mass in Prepubertal Girls: A Combined Cross-Sectional and 3-Year Longitudinal Study

This study evaluates the effect on the skeleton of physical activity from age 9 to 16. In 42 girls and 44 boys, bone mass and bone size were evaluated longitudinally by dual-energy X-ray absorptiometry (DXA) from ages 13 to 16. Physical activity from ages 9 to 13 was cross-sectionally evaluated at baseline (age 13). Girls with high physical activity from ages 9 to 13 at baseline had higher femoral neck bone mineral content (FN BMC; g) (P = 0.07), higher FN areal bone mineral density (FN aBMD; g/cm2), and higher FN volumetric BMD (FN vBMD; g/cm3) (both P <0.05) compared with girls of low activity. FN width (cm) and head aBMD (an unloaded region) showed no differences when comparing the two groups. Three years of further high and low activity (from ages 13 to 16) did not yield any increased differences between the two groups. Boys with high physical activity from ages 9 to 13, had at baseline higher FN BMC, FN aBMD, and FN width (all P <0.05) compared with boys with low activity. FN vBMD and head aBMD showed no differences when comparing the two groups. Three years of further high and low activity did not yield any increased differences between the two groups. We conclude that exercise may yield skeletal benefits before age 13, and that 3 years of continued high or low level activity up to age 16 did not yield any increased differences in bone size or bone mass in either girls or boys.